DISPATCHES Jakarta, Indonesia; and Hechi City, China, for 12 months Salmonella to identify typhoid and paratyphoid cases from specific populations at high risk (Table). None of the sites had spe- Paratyphi A Rates, cific enteric fever control programs in the past. Hechi City, China, is located in Guangxi Zhuang Autonomous Region Asia where Vi vaccines had been used in the past (8,9); howev- er, no such intervention had taken place in Hechi City. The R. Leon Ochiai,* XuanYi Wang,* closest county with a vaccination program was ≈80 km Lorenz von Seidlein,* Jin Yang,† away and vaccinated only students (29,000 doses in 2001). Zulfiqar A. Bhutta,‡ Sujit K. Bhattacharya,§ During the surveillance period, persons with fever who Magdarina Agtini,¶ Jacqueline L. Deen,* lived in each study area were requested to visit participat- John Wain,# Deok Ryun Kim,* Mohammad Ali,* ing healthcare providers. We collected 5–10 mL blood Camilo J. Acosta,* Luis Jodar,* from adults with fever >3 days’ duration into Bactec bot- and John D. Clemens* tles (Becton Dickinson, Franklin Lakes, NJ, USA). We Little is known about the causes of enteric fever in collected 3–8 mL from children with fever >3 days’ dura- Asia. Most cases are believed to be caused by Salmonella tion into Pediatric Bactec bottles. The bottles were incu- enterica serovar Typhi and the remainder by S. Paratyphi bated at 37°C for 7–10 days and visually checked for A. We compared their incidences by using standardized growth every day. Bottles were subcultured on methods from population-based studies in China, MacConkey agar on days 1, 2, 4, and 7 or when turbidity Indonesia, India, and Pakistan. was detected. Suspected colonies were screened by using Kligler iron agar, sulfide-indole-motility medium, urea nteric fever still causes substantial illness and death in agar, and citrate. Colonies that showed biochemical reac- Emany parts of the world, especially in poorer nations. tions suggestive of salmonellae were confirmed serologi- Salmonella enterica serovar Typhi is believed to cause cally by Felix-Widal tube agglutination test with specific most enteric fever episodes, and a smaller portion are O and H antisera (Becton Dickinson). All Salmonella iso- caused by S. Paratyphi (1–3). This assumption, however, lates were confirmed at a reference laboratory (University may no longer be true. Since 1999, more S. Paratyphi A of Oxford, Wellcome Trust Clinical Research Unit, Ho Chi than S. Typhi strains have been isolated in the province of Minh City, Vietnam). Guangxi, southeastern China (4). Increasing isolation rates Incidence rates were calculated by using age-specific of S. Paratyphi A has also been reported from India (5). denominators of the population living in the catchment This finding has 2 major implications for the prevention of area based on the study census. We assumed that each per- enteric fever. First, licensed typhoid fever vaccines (Vi son living in the study area contributed 12 months of per- polysaccharide and live oral Ty21a) do not protect against son-time to the denominator. The number of disease infections caused by S. Paratyphi A, and they may become episodes in eligible individuals was used as the numerator. less useful in controlling enteric fever in regions of Asia. Each study received individual approval from the local Second, transmission and risk factors for S. Typhi and S. ethical committees, the institutional review board of the Paratyphi are different in Indonesia (6), so reduction International Vaccine Institute (Seoul, Korea), and the strategies effective against S. Typhi may not protect Secretariat Committee for Research Involving Human against S. Paratyphi. Since little is known about the current Subjects, World Health Organization (Geneva, cause of enteric fever in Asia, we compared S. Typhi and Switzerland). S. Paratyphi A incidence from study sites in China, During the surveillance period, 285 S. Typhi episodes Indonesia, India, and Pakistan by using standardized epi- and 84 S. Paratyphi A episodes were detected at the 4 sites demiologic and laboratory methods (7). (Table). In Indonesia, 14% of enteric fever episodes were caused by S. Paratyphi A, in Pakistan 15%, in India 24%, The Study and in China 64% (Figure). The highest S. Typhi incidence After a baseline census, surveillance was conducted in was observed in Pakistan (394/100,000/year), and the low- study sites in Karachi, Pakistan; Calcutta, India; North est S. Typhi incidence was found in China (15.2/100,000/year). The highest S. Paratyphi A incidence *International Vaccine Institute, Seoul, Korea; †Guangxi Centers was also seen in Pakistan (72/100,000/year), and the low- for Disease Control and Prevention, Nanning, People’s Republic est S. Paratyphi A incidence was seen in Indonesia of China; ‡Aga Khan University, Karachi, Pakistan; §National (13.7/100,000/year). Institute of Cholera and Enteric Diseases, Kolkata, India; ¶National Institute of Health, Research and Development, Jakarta, Indonesia; and #Sanger Institute, Cambridge, United Kingdom 1764 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 11, No. 11, November 2005 Salmonella Paratyphi A Rates, Asia Conclusions rate of S. Paratyphi A is possibly caused by an increase in The perception that a small proportion of enteric fever the number of cases of enteric fever caused by S. cases are caused by S. Paratyphi A is probably no longer Paratyphi A rather than any bias toward blood culture– true in many regions of Asia, especially in southeast China, positive disease. where S. Paratyphi A is already more frequently isolated Besides the limitation that our studies only describe a than is S. Typhi. This finding could be signaling the emer- 12-month period, the population varied between sites. In gence of S. Paratyphi A as a pathogen in Asia. Comparison Pakistan, only children 2–16 years of age were included. of S. Paratyphi A incidence during the last decade is need- As S. Paratyphi A infections are more frequently observed ed to prove this hypothesis. However, none of the sites in adults, including older patients in surveillance may have comparable surveillance data on S. Paratyphi A over increase S. Paratyphi A incidence rates reported from time. An alternative explanation is that the incidence of S. Pakistan. Typhi is decreasing. Previous reports from vaccine trials In China and India, countries with the largest popula- have shown successful control of S. Typhi but no changes tions in the world, S. Paratyphi A is the causal agent for a in the incidence of S. Paratyphi A (8,10,11). Nonetheless, substantial proportion of enteric fever episodes that can- the reversal of the proportion of S. Typhi and S. Paratyphi not be distinguished clinically from typhoid fever A infections in Hechi City, China, is unlikely to be the episodes. While similar treatment strategies may work for result of typhoid fever control in other counties, consider- both organisms, future enteric fever prevention strategies ing the distance and oral-fecal transmission route of S. in Asia must focus on S. Paratyphi A as well as on S. Typhi and S. Paratyphi A. Typhi, especially when considering the emergence of Economic growth in Asia has also resulted in improved drug-resistant strains (13–15). Future vaccination strate- water supply, sanitation, and hygiene; however, we have gies should include bivalent vaccines that protect against no reason to assume selective reduction only for transmis- S. Typhi as well as S. Paratyphi A. Otherwise, the protec- sion of S. Typhi. The incidence of typhoid fever per tive effectiveness of typhoid fever vaccines (Vi, Ty21a) 100,000 in the different countries follows the same pattern against enteric fever may diminish, which could result in as mean gross national income (2003) and the mortality a loss of public confidence and decrease public willing- ranking for children <5 years (12). ness to be vaccinated. The sensitivity of blood culture for S. Typhi is well described, but little is known about S. Paratyphi A. Acknowledgments Bacterial loads during infection are probably similar for We are grateful for the support for this work received from both S. Typhi and S. Paratyphi A (J. Wain, unpub. data). C.M. Galindo, A.L. Page, M.C. Danovaro-Holliday, and J. Farrar. Furthermore, S. Paratyphi A had been rarely isolated in We acknowledge the hard work from the laboratory personnel these regions, which suggests that the increase in isolation from each site, M.L. Wang, D. Alam, S. Dutta, and Murad. We thank an anonymous reviewer for valuable suggestions. This work was supported by the Diseases of the Most Impoverished Program, funded by the Bill and Melinda Gates Foundation and coordinated by the International Vaccine Institute. Mr Ochiai is associate research scientist at the International Vaccine Institute, coordinating the Diseases of the Most Impoverished Typhoid Fever Program. His specialty is epidemi- ology and international health, and his current area of interest is vaccine-preventable disease epidemiology. Figure. Incidence of Salmonella enterica serovar Typhi and S. Paratyphi A in 4 Asian countries. Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 11, No. 11, November 2005 1765 DISPATCHES References 9. Yang HH, Kilgore PE, Yang LH, Park JK, Pan YF, Kim Y, et al. An outbreak of typhoid fever, Xing-An County, People’s Republic of 1. Herikstad H, Motarjemi Y, Tauxe RV. Salmonella surveillance: a China, 1999: estimation of the field effectiveness of Vi polysaccha- global survey of public health serotyping. Epidemiol Infect. ride typhoid vaccine. J Infect Dis. 2001;183:1775–80. 2002;129:1–8. 10. Bodhidatta L, Taylor DN, Thisyakorn U, Echeverria P. Control of 2. Crump JA, Youssef FG, Luby SP, Wasfy MO, Rangel JM, Taalat M, typhoid fever in Bangkok, Thailand, by annual immunization of et al. Estimating the incidence of typhoid fever and other febrile ill- schoolchildren with parenteral typhoid vaccine.